Indoleamine 2,3-dioxygenase-1 (IDO1) catabolizes the L-tryptophan (Trp) to yield L-N-formylkynurenine (Kyn), which is the initial and rate-limiting step in Trp degradation pathway. IDO1 is expressed in a variety of tissues and particularly high level expression observed in placenta of pregnant females, various human tumor cells, and dendritic cells that localize to the tumor-draining lymph nodes [1-3]. Increasing in vivo and in vitro pieces of evidence implicated that IDO1 is involved in immune escape of tumor cells, and blockage of its activity can directly increase the ability of tumor-bearing mice to reject tumors [2,4-7]. Recent studies demonstrated that the expression level of IDO increased in various tumors such as in lungs, prostate, and pancreas, lymphoma, and breast cancers. It is reported that patients with high level of IDO1 expression were correlated with later clinical phases and larger tumors and indicated a worse prognosis in various cancers such as diffuse large B-cell lymphoma and chronic lymphocytic leukemia [8-10]. Currently, two IDO1 inhibitors 1-methyl-D-tryptophan and INCB024360 are used in phase II clinical trials for the treatment of breast cancer and melanoma, respectively [11].
Molecular imaging methods such as positron emission tomography (PET) have the potential to generate IDO1 expression profile in vivo and provide valuable information on how the IDO pathway responds to the immune-modulating therapies. α-[11C] methyl-L-tryptophan (α-11C-AMT), an IDO1 substrate, has been reported to be associated with the IDO1 expression levels in the brain and lung tumors [12,13]. However, IDO1 only was involved in the first step of the kynurenine pathway, while increased α-11C-AMT uptake by cells is a complicated issue because of many other enzymes involved in tryptophan transportation and metabolism pathway. Therefore, there is an urgent need to develop a specific PET imaging agent targeted to IDO1 for cancer imaging.